1. Field of the Invention
This invention relates to new anthracycline antibiotics and to their production and recovery.
2. Description of the Prior Art
A number of anthracycline glycosides have been described in the literature. Among them, daunomycin and adriamycin are particularly being watched with keen interest in the field of cancer chemotherapy and have already been applied clinically for human cancers.
Preparation of adriamycin by fermentation of S. peuceticus var. caesius is disclosed in U.S. Pat. No. 3,590,028. Chemical conversion of daunomycin to adriamycin is taught in U.S. Pat. No. 3,803,124.
Daunomycin (produced by fermentation of S. peuceticus in U.K. Pat. No. 1,003,383) may be the same as Rhone-Poulenc's 13,057 R.P. (formerly rubidomycin and now daunorubicin; see U.K. Pat. Nos. 985,598, 1,188,262 and 1,241,750 and U.S. Pat. No. 3,616,242) and is probably identical to Ciba's danubomycin disclosed in U.S. Pat. No. 3,092,550 and U.K. Pat. No. 901,830. See also U.S. Pat. No. 3,686,163 on dihydrodaunomycin.
Cinerubin A and cinerubin B, glycosides of the aglycone .epsilon.-pyrromycinone, are disclosed in U.K. Pat. No. 846,130 [see also U.S. Pat. No. 3,864,480 and Keller-Schierlein, et al., Antimicrobial Agents and Chemotherapy, page 68 (1970) and Chemical Abstracts, 54, 1466i (1960)].
The anthracycline glycoside carminomycin described in J. Antibiotics 27:254-259 (1974), in West German Specification 2,362,707 and in J. Amer. Chem. Soc. 97(20):5955-5956 (1975) has been reported to be active against several animal tumor systems.
Trypanomycin is described in Antimicrobial Agents and Chemotherapy 1:385-391 (1972) as having strong antiprotozoal activity. It has an aglycone similar to but not identical with .epsilon.-pyrromycinone.
The antibiotic pyrromycin disclosed in Chem. Ber. 92:1904-1909 (1959) contains the aglycone .epsilon.-pyrromycinone and the glycosidic sugar rhodosamine.
For further illustrative and summary disclosures of anthracycline antibiotics see Index of Antibiotics from Actinomycetes, Hamao Umezawa, Editor-in-Chief, University Park Press, State College, Pennsylvania, U.S.A. (1967) as follows:
______________________________________ Antibiotic Page Number ______________________________________ Aklavin 111 Cinerubin A 220 Cinerubin B 221 Danubomycin 242 Daunomycin 243 Pyrromycin 542 Rhodomycin A,B 561 Rubidomycin 574 ______________________________________
The textbook Antibiotics, Volume 1, Mechanism of Action, edited by David Gottlieb and Paul D. Shaw, SpringerVerlag New York, Inc., N.Y., N.Y. (1967) at pages 190-210 contains a review by A. DiMarco entitled Daunomycin and Related Antibiotics.
Information Bulletin, No. 10, International Center of Information of Antibiotics, in collaboration with WHO, December, 1972, Belgium, reviews anthracyclines and their derivatives.